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1.
  • Dock, Hua, et al. (författare)
  • DNA Methylation Inhibitor Zebularine Confers Stroke Protection in Ischemic Rats
  • 2015
  • Ingår i: TRANSLATIONAL STROKE RESEARCH. - Springer Verlag (Germany). - 1868-4483. ; 6:4, s. 296-300
  • Tidskriftsartikel (refereegranskat)abstract
    • 5-Aza-deoxycytidine (5-aza-dC) confers neuroprotection in ischemic mice by inhibiting DNA methylation. Zebularine is another DNA methylation inhibitor, less toxic and more stable in aqueous solutions and, therefore more biologically suitable. We investigated Zebularines effects on brain ischemia in a rat middle cerebral artery occlusion (MCAo) model in order to elucidate its therapeutic potential. Male Wistar wild-type (WT) rats were randomly allocated to three treatment groups, vehicle, Zebularine 100 mu g, and Zebularine 500 mu g. Saline (10 mu L) or Zebularine (10 mu L) was administered intracerebroventricularly 20 min before 45-min occlusion of the middle cerebral artery. Reperfusion was allowed after 45-min occlusion, and the rats were sacrificed at 24-h reperfusion. The brains were removed, sliced, and stained with 2 % 2,3,5-triphenyltetrazolium chloride (TTC) before measuring infarct size. Zebularine (500 mu g) reduced infarct volumes significantly (p less than 0.05) by 61 % from 20.7 +/- 4.2 % in the vehicle treated to 8.1 +/- 1.6 % in the Zebularine treated. Zebularine (100 mu g) also reduced infarct volumes dramatically by 55 to 9.4 +/- 1.2 %. The mechanisms behind this neuroprotection is not yet known, but the results agree with previous studies and support the notion that Zebularine-induced inhibition of DNA methyltransferase ameliorates ischemic brain injury in rats.
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2.
  • Hilke, Susanne, et al. (författare)
  • Estrogen induces a rapid increase in galanin levels in female rat hippocampal formation : possibly a nongenomic/indirect effect
  • 2005
  • Ingår i: European Journal of Neuroscience. - 0953-816X. ; 21:8, s. 2089-2099
  • Tidskriftsartikel (refereegranskat)abstract
    • Administration of 17β-estradiol to ovariectomized rats increased the concentrations of galanin-like immunoreactivity (LI) in the hippocampal formation by 215% (P < 0.001) within 1 h. An increase of 125% (P < 0.05) was observed in the same brain region in the proestrous phase of a normal estrous cycle. Tamoxifen® did not block the 17β-estradiol-induced increase in the concentration of galanin-LI but resulted in a 62% decrease in the hypothalamus within 1 h. In vivo microdialysis in the dorsal hippocampal formation showed a decrease of extracellular galanin-LI (P < 0.001) 1−2 h after treatment with 17β-estradiol, indicating a decreased release of galanin. For comparision, we studied the concentrations of neuropeptide Y, which were not influenced significantly in any of the regions studied. Taken together our results suggest that 17β-estradiol inhibits galanin release, presumably from noradrenergic nerve terminals, and primarily via a nongenomic/indirect action, not necessarily involving the classical nuclear receptors ER-α or ER-β. These rapid estrogen-induced changes in galanin release could influence transmitter signalling and plasticity in the hippocampal formation.
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3.
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4.
  • Ingberg, Edvin, et al. (författare)
  • Elevated body swing test after focal cerebral ischemia in rodents: : methodological considerations
  • 2015
  • Ingår i: BMC neuroscience (Online). - BioMed Central / Springer Verlag (Germany). - 1471-2202. ; 16:50
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The elevated body swing test (EBST) is a behavioral test used to evaluate experimental stroke in rodents. The basic idea is that when the animal is suspended vertically by the tail, it will swing its head laterally to the left or right depending on lesion side. In a previous study from our lab using the EBST after middle cerebral artery occlusion (MCAo), rats swung contralateral to the infarct day 1 post-MCAo, but ipsilateral day 3 post-MCAo. This shift was unexpected and prompted us to perform the present study. First, the literature was systematically reviewed to elucidate whether a similar shift had been noticed before, and if consensus existed regarding swing direction. Secondly, an experiment was conducted to systematically investigate the suggested behavior. Eighty-three adult male and female Sprague-Dawley rats were subjected to MCAo or sham surgery and the EBST was performed up to 7 days after the lesion. Results: Both experimentally and through systematic literature review, the present study shows that the direction of biased swing activity in the EBST for rodents after cerebral ischemia can differ and even shift over time in some situations. The EBST curve for females was significantly different from that of males after the same occlusion time (p = 0.023). Conclusions: This study highlights the importance of adequate reporting of behavioral tests for lateralization and it is concluded that the EBST cannot be recommended as a test for motor asymmetry after MCAo in rats.
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5.
  • Ingberg, Edvin, et al. (författare)
  • Methods for long-term 17 beta-estradiol administration to mice
  • 2012
  • Ingår i: General and Comparative Endocrinology. - Elsevier. - 0016-6480. ; 175:1, s. 188-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17 beta-estradiol. However, a thorough assessment of the methods for long-term administration of 17 beta-estradiol to mice is lacking. The fact that 17 beta-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17 beta-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 mu g 17 beta-estradiol/mL sesame oil), or a novel peroral method (56 mu g 17 beta-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17 beta-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within - except on one occasion - the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17 beta-estradiol, superior to the widely used commercial pellets.
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6.
  • Isaksson, Ida-Maria, et al. (författare)
  • Methods for 17 beta-oestradiol administration to rats
  • 2011
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Informa Healthcare. - 0036-5513. ; 71:7, s. 583-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies indicate that the beneficial or harmful effects of oestrogens in stroke are dose-dependent. Rats are amongst the most frequently used animals in these studies, which calls for thoroughly validated methods for administering 17 beta-oestradiol to rats. In an earlier study we characterised three different administration methods for 17 beta-oestradiol over 42 days. The present study assesses the concentrations in a short time perspective, with the addition of a novel peroral method. Female Sprague-Dawley rats were ovariectomised and administered 17 beta-oestradiol by subcutaneous injections, silastic capsules, pellets and orally (in the nut-cream Nutella (R)), respectively. One group received 17 beta-oestradiol by silastic capsules without previous washout time. Blood samples were obtained after 30 minutes, 1, 2, 4, 8, 12, 24, 48 and 168 hours and serum 17 beta-oestradiol (and oestrone sulphate in some samples) was subsequently analysed. For long-term characterisation, one group treated perorally was blood sampled after 2, 7, 14, 21, 28, 35 and 42 days. At sacrifice, uterine horns were weighed and subcutaneous tissue samples were taken for histological assessment. The pellets, silastic capsule and injection groups produced serum 17 beta-oestradiol concentrations that were initially several orders of magnitude higher than physiological levels, while the peroral groups had 17 beta-oestradiol levels that were within the physiological range during the entire experiment. The peroral method is a promising option for administering 17 beta-oestradiol if physiological levels or similarity to womens oral hormone therapy are desired. Uterine weights were found to be a very crude measure of oestrogen exposure.
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7.
  • Isaksson, Ida-Maria, et al. (författare)
  • Methods for 17β-oestradiol administration to rats
  • 2011
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Informa Healthcare. - 0036-5513. ; 71:7, s. 583-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies indicate that the beneficial or harmful effects of oestrogens in stroke are dose-dependent. Rats are amongst the most frequently used animals in these studies, which calls for thoroughly validated methods for administering 17β-oestradiol to rats. In an earlier study we characterised three different administration methods for 17β-oestradiol over 42 days. The present study assesses the concentrations in a short time perspective, with the addition of a novel peroral method. Female Sprague-Dawley rats were ovariectomised and administered 17β-oestradiol by subcutaneous injections, silastic capsules, pellets and orally (in the nut-cream Nutella®), respectively. One group received 17β-oestradiol by silastic capsules without previous washout time. Blood samples were obtained after 30 minutes, 1, 2, 4, 8, 12, 24, 48 and 168 hours and serum 17β-oestradiol (and oestrone sulphate in some samples) was subsequently analysed. For long-term characterisation, one group treated perorally was blood sampled after 2, 7, 14, 21, 28, 35 and 42 days. At sacrifice, uterine horns were weighed and subcutaneous tissue samples were taken for histological assessment. The pellets, silastic capsule and injection groups produced serum 17β-oestradiol concentrations that were initially several orders of magnitude higher than physiological levels, while the peroral groups had 17β-oestradiol levels that were within the physiological range during the entire experiment. The peroral method is a promising option for administering 17β-oestradiol if physiological levels or similarity to women's oral hormone therapy are desired. Uterine weights were found to be a very crude measure of oestrogen exposure.
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8.
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9.
  • Rugarn, Olof, et al. (författare)
  • Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain
  • 1999
  • Ingår i: Peptides. - 0196-9781. ; 20:6, s. 743-748
  • Tidskriftsartikel (refereegranskat)abstract
    • Concentrations of immunoreactive galanin were compared in eight gross brain regions of ovariectomized female rats treated with either estradiol, estradiol + progesterone, estradiol + norethisterone, or placebo. Higher concentrations with estradiol treatment compared with placebo were found in the pituitary (357%), frontal cortex (162%), occipital cortex (174%), hippocampus (170%), and median eminence (202%). A more profound difference with addition of progesterone or norethisterone was seen in the pituitary (529% and 467%, respectively). Sex steroids, particularly estradiol, modulate galanin concentrations not only in reproductive, but also in nonreproductive, brain regions.
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10.
  • Rugarn, Olof, et al. (författare)
  • Sex differences in neuropeptide distribution in the rat brain
  • 1999
  • Ingår i: Peptides. - 0196-9781. ; 20:1, s. 81-86
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated possible sex differences in the regional concentrations of neuropeptides in the rat brain. Immunoreactive neurotensin (NT), neurokinin A (NKA), galanin (GAL), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) were measured by radioimmunoassay in frontal cortex, occipital cortex, hippocampus, striatum, hypothalamus and pituitary in male and female pre- and postpubertal rats. Sex differences were found for NPY (p < 0.001), NT (p < 0.01) and GAL (p < 0.05), in particular in hippocampus, striatum, hypothalamus and pituitary, but not for CGRP, SP and NKA. Results from analysis of neuropeptides in one sex may not be entirely applicable to the other.
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